Serial imaging and arthroscopy provides evidence that intra-articular cell therapy changes the trajectory of osteoarthritis
[um_loggedin show_lock=yes]Authors: Flynn C, Hurtig M. Jeong SY*
Affiliations: University of Guelph, University of Toronto, *Medipost LLC, Seoul, Korea
Introduction: Difficulty in staging osteoarthritis (OA) progression requires long expensive studies. In this study we show that non-invasive assessment of OA trajectory can detect changes in the rate of OA progression after intra-articular human umbilical origin stromal cell therapy in a sheep model.
Hypothesis/Objectives: Our objective was to develop methods that would allow practical and economic real time analysis of osteoarthritis progression in animals with thin cartilage (such as the dog and sheep) which makes these species less amenable to MRI assessments.
Materials and Methods: Four groups of 11 female adult sheep underwent arthroscopic meniscal release to induce OA in one stifle joint. Twelve weeks later these four groups received either intra-articular saline, hyaluronate carrier, low dose (1M) human umbilical cells, or high dose (5M) cells. Change in joint shape was measured using OSiriX software. A linear mixed model was used to compare the trajectory of shape change and subchondral sclerosis among the groups. Serial diagnostic arthroscopy was used to assess cartilaginous changes and synovitis. We then used ordinal logistic regression used to investigate the association between shape change and sclerosis.
Results: A linear mixed model demonstrated significant change in medial compartment length and width over time (p< 0.05) for all four groups. Group allocation alone did not have a significant main effect on shape change but there was a significant interaction between time and group (p<.001) when treated groups were compared to saline and HA controls. there was significant effect of group (p<.001) when comparing MTP length between both the low-dose and high-dose groups and pooled controls. A significant association between sclerosis and medial compartment shape change was present in the saline and HA groups that did not receive cell therapy. Conclusions: The induction of osteoarthritic lesions with meniscal release model can be followed using non- and minimally-invasive procedures. Our statistical modeling provides evidence that change in joint morphology can be used as an imaging biomarker for OA progression. Changes in the OA trajectory between pooled saline and HA controls versus treated groups suggests protection against OA progression with cell therapy.
Acknowledgements, Funding, and Conflicts of Interest: Funded by: The Korean Food and Drug Safety Administration. Cells were the generous gift of Medipost LLC.[/um_loggedin]